Initial response to the COVID-19 pandemic on real-life well-being, social contact and roaming behavior in patients with schizophrenia, major depression and healthy controls: A longitudinal ecological momentary assessment study

The COVID-19 pandemic strongly impacted people\u27s daily lives. However, it remains unknown how the pandemic situation affects daily-life experiences of individuals with preexisting severe mental illnesses (SMI). In this real-life longitudinal study, the acute onset of the COVID-19 pandemic in Germany did not cause the already low everyday well-being of patients with schizophrenia (SZ) or major depression (MDD) to decrease further. On the contrary, healthy participants’ well-being, anxiety, social isolation, and mobility worsened, especially in healthy individuals at risk for mental disorder, but remained above the levels seen in patients. Despite being stressful for healthy individuals at risk for mental disorder, the COVID-19 pandemic had little additional influence on daily-life well-being in psychiatric patients with SMI. This highlights the need for preventive action and targeted support of this vulnerable population

Functional polymorphism in the neuropeptide Y gene promoter (rs16147) is associated with serum leptin levels and waist-hip ratio in women

OBJECTIVE: The neuropeptide-Y (NP-Y) gene is a strong candidate gene in the pathophysiology of obesity-linked behavior, and several single-nucleotide polymorphisms of NP-Y have already been linked to body weight and appetite. However, the results from current studies remain inconclusive. The aim of the present study was to test whether a certain functional genetic variant (SNP rs16147) in the NP-Y promoter gene is associated with serum leptin levels and body fat distribution. METHOD: We genotyped and measured the serum leptin levels of the NP-Y rs16147 polymorphism in 1,097 Caucasian subjects in the context of a population-based, case-control multicenter study. We measured weight, height and waist circumference, from which we then calculated BMI and waist-to-hip ratio (WHR). RESULTS: We found the CT-genotype of the SNP rs16147 to be significantly associated with lower WHRs and higher serum leptin levels in women, compared to homozygote gene carriers. No association between rs16147, WHR and serum leptin levels was found in men. CONCLUSION: Our results provide evidence that the functionally relevant SNP in the NP-Y promoter gene affects body fat distribution and serum leptin levels in women, pointing towards possible behavioral effects of NPY in obesity

Essays in Development and Environmental Economics

This dissertation discusses three questions of development and environmental economics. First, it assesses the impact of mineral mining on the health and wealth of households in local communities across 44 developing countries, using micro data. Secondly, it presents evidence from a randomized controlled trial on the cost-shared provision of well-water tests for arsenic. Finally, it analyzes measurement error in a satellite night light data product widely used in development research, and investigates the scope for using the data in very high spatial resolution

Polycystic Ovary Syndrome in Patients with Epilepsy

Eine erhöhte Prävalenz von endokrinologischen Störungen bei Epilepsiepatientinnen wird in diversen Studien in Abhängigkeit von der antikonvulsiven Medikation oder dem Epilepsiesyndrom diskutiert. In den letzten Jahren ist das Antiepileptikum Valproinsäure mit der Entstehung des Polyzystischen Ovariensyndroms (PCOS) bei Epilepsiepatientinnen in Verbindung gebracht worden. Je nach Einbeziehung des Ultraschallbefundes finden sich in der Literatur erhebliche Prävalenzunterschiede für ein PCOS bei Epilepsiepatientinnen. Ziel der vorliegenden Arbeit war es, die Häufigkeit des PCOS und dessen mögliche Assoziation mit der antikonvulsiven Medikation und/oder der Epilepsieart in einem unselektierten Patientengut der Epilepsiesprechstunde der Neurologischen Klinik und Poliklinik der Charité/Campus Virchow-Klinikum in einer Querschnittsuntersuchung zu untersuchen. Es wurden 54 bereits antiepileptisch mit Valproinsäure, Carbamazepin oder Lamotrigin in Monotherapie behandelte Patientinnen untersucht, wovon 35 Patientinnen ein weiteres Mal nach zwei Monaten und davon 20 Patientinnen ein weiteres Mal nach sechs Monaten untersucht wurden. Bei 7 der 54 Patientinnen fand schon eine Untersuchung vor der ersten Medikamenteneinnahme statt, sowie drei weitere (einmal nach zwei, nach sechs, sowie nach zwölf Monaten) in Form einer zusätzlichen Longitudinalstudie statt. Unsere Daten zeigen weder eine eindeutige Korrelation eines PCOS nach den verschiedenen Definitionen und/oder dem sonographischen Nachweis polyzystischer Ovarien mit der antiepileptischen Medikation noch mit der Epilepsieart. Die Häufigkeit eines PCOS in der Stichprobe hing deutlich von den verwendeten Definitionskriterien ab, welche in erster Linie dadurch bestimmt waren, ob der Ultraschallbefund in die Definition eingeschlossen war. In der vorliegenden Untersuchung konnten Prävalenzunterschiede von 4% bis 63% gezeigt werden. Der Ultraschallbefund zeigte sich bei 14% der Patientinnen in den Folgeuntersuchungen inkonsistent.Epilepsy has been associated with an increased frequency of reproductive endocrine disorders including polycystic ovary syndrome (PCOS). Some study groups claim that epilepsy itself plays a pathogenic role, whereas others propose that PCOS may be attributable to the use of antiepileptic drugs (AEDs), particularly sodium valproate (VPA). Estimates regarding the prevalence of PCOS in this patient group vary, among other reasons, because of different definitions of PCOS. The aim of the present cross-sectional and longitudinal study was to test the prevalence of PCOS in female patients with epilepsy and to investigate the possible association between epilepsy and/or AEDs and PCOS. The study group included 54 female patients with epilepsy aged 18-45 years who were treated with valproate (n=31), carbamazepine (n=15) or lamotrigine (n=8) in monotherapy. Relevant clinical and biochemical paramaters were testet and all women underwent a transvaginal ovarian ultrasound assessment. The prevalence of PCOS following different definitions was determinated. Follow-up evaluations were done in 35 of these patients after 2 months, and in 20 of them after 6 months. 7 of these women were also evaluated before antiepileptic medication. No statistically significant association was found between AEDs, epilepsy and PCOS or the single endocrine or clinical parameters of the syndrome. The variance of the prevalence of PCOS according to the different definitions was very high (4-63%). The finding of ultrasound diagnosed polycystic ovaries was inconsistent in 14% of the patients at the follow-up evaluations

Essays in Development and Environmental Economics

This dissertation discusses three questions of development and environmental economics. First, it assesses the impact of mineral mining on the health and wealth of households in local communities across 44 developing countries, using micro data. Secondly, it presents evidence from a randomized controlled trial on the cost-shared provision of well-water tests for arsenic. Finally, it analyzes measurement error in a satellite night light data product widely used in development research, and investigates the scope for using the data in very high spatial resolution

Intraperitoneal atrial natriuretic peptide attenuates anxiety-related behaviour during alcohol withdrawal in mice

Converging evidence from both preclinical and clinical studies suggests atrial natriuretic peptide (ANP) as a potential target for treatment of alcohol withdrawal and dependence. Since ANP tightly interacts with hypothalamic-pituitary-adrenocortical (HPA) axis activity, especially the modulation of stress-related anxiety during alcohol withdrawal might mediate these effects. We have now evaluated the anxiolytic activity of intraperitoneal ANP application during alcohol withdrawal in alcohol-habituated mice (C57/Bl6J). Anxiety related behaviour was attenuated during ethanol withdrawal following application of ANP (60 μg/kg) vs. saline. Our results support that anxiolytic effects of ANP mediate ANP-related gene effects with clinical data on withdrawal symptomatology

Real-life behavioral and neural circuit markers of physical activity as a compensatory mechanism for social isolation

Social isolation and loneliness pose major societal challenges accelerated by the coronavirus disease 2019 pandemic, especially for mental health. In this cohort study using accelerometry, electronic diaries and neuroimaging in a community-based sample of 317 young adults, we show that people felt affectively worse when lacking social contact, but less so when engaging in physical activity. This putative compensatory mechanism was present even at small physical activity doses and was pronounced in individuals with higher brain functional connectivity within the default mode network signaling risk for depression. Social-affective benefits of movement were higher in people showing exacerbated loneliness and were replicated throughout the pandemic. These findings extend the state of knowledge on the dynamic interplay of social contact and physical activity in daily life identifying an accessible protective strategy to mitigate the negative effects of social isolation, particularly among at-risk individuals, which comes with the potential to improve public health in the post-pandemic world

Effects of D-cycloserine on extinction of mesolimbic cue reactivity in alcoholism : a randomized placebo-controlled trial

Rationale Mesocorticolimbic reactivity to alcohol-associated cues has been shown to be associated with relapse to renewed drinking and to be decreased by cue-exposure-based extinction training (CET). Evidence from preclinical studies suggests that the extinction of conditioned alcohol-seeking behavior might be facilitated by drugs increasing N-methyl-d-aspartate (NMDA) receptor-associated memory consolidation. Objectives In this study, we assessed the efficacy of CET treatment supplemented with the partial NMDA-receptor agonist d-cycloserine (DCS) at reducing mesolimbic cue reactivity (CR), craving, and relapse risk in alcoholism. Methods In a randomized, placebo-controlled, double-blind study, we recruited 76 recently detoxified abstinent alcohol-dependent patients. Thirty-two (16 DCS, 16 placebo) patients showed cue-induced ventral-striatal activation measured with functional magnetic resonance imaging (fMRI) prior to treatment and were thus included in the efficacy analyses. After inpatient detoxification, patients underwent nine sessions of CET spaced over 3 weeks, receiving either 50 mg DCS or placebo 1 h prior to each CET session. FMRI was conducted before treatment and 3 weeks after treatment onset. Results Following treatment with CET plus DCS, cue-induced brain activation in the ventral and dorsal striatum was decreased compared to treatment with CET plus placebo. Elevated posttreatment ventral striatal CR and increased craving (assessed using the Obsessive Compulsive Drinking Scale) were associated with increased relapse risk. Conclusions DCS was shown to augment the effect of CET for alcohol-dependent subjects. The interaction between craving and ventral-striatal CR on treatment outcome suggests that CET might be especially effective in patients exhibiting both high craving and elevated CR

Identifying the gap between need and intervention for alcohol use disorders in Europe

A literature review of existing research on the prevalence of alcohol use disorders (AUDs) and availability of alcohol interventions in Europe was conducted. The review also explored what is known about the gap between need and provision of alcohol interventions in Europe. Methods The review search strategy included: (i) descriptive studies of alcohol intervention systems in Europe; (ii) studies of alcohol service provision in Europe; and (iii) studies of prevalence of AUD and alcohol needs assessment in Europe. Results Europe has a relatively high level of alcohol consumption and the resulting disabilities are the highest in the world. Most research on implementation of alcohol interventions in Europe has been restricted to screening and brief interventions. Alcohol needs assessment methodology has been developed but has not been applied in comparative studies across countries in Europe. Conclusions This review points to key gaps in knowledge related to alcohol interventions in Europe. There is a lack of comparative data on variations in alcohol treatment systems across European countries and there is also a lack of comparative data on the prevalence of alcohol use disorders across European countries and the relative gap between need and access to treatment. The forthcoming Alcohol Measures for Public Health Research Alliance (AMPHORA) research projectwork package on ‘Early identification and treatment’ aims to address these gaps

Epigenetic alteration of the dopamine transporter gene in alcohol-dependent patients is associated with age

Chronic alcohol abuse and dependence are associated with dysfunctional dopaminergic neurotransmission in mesocorticolimbic circuits. Genetic and environmental factors have been shown to modulate susceptibility to alcohol dependence, and both may act through epigenetic mechanisms that can modulate gene expression, e.g. DNA methylation at CpG sites. Recent studies have suggested that DNA methylation patterns may change over time. However, few data are available concerning the rate of these changes in specific genes. A recent study found that hypermethylation of the promoter of the dopamine transporter (DAT) gene was positively correlated with alcohol dependence and negatively correlated with alcohol craving. The aim of the present study was to replicate these findings in a larger sample of alcohol-dependent patients and population-based controls matched for age and sex. No difference in methylation level was observed between patients and controls, and no difference in methylation level was observed before and after alcohol withdrawal in patients. However, patients with more severe craving showed a trend towards lower DAT methylation levels (P = 0.07), which is consistent with previous findings. Furthermore, in our overall sample, DAT methylation levels increased with age. Interestingly, a separate analysis of patients suggested that this finding was mainly driven by the patient group. Although the present data do not clarify whether chronic alcohol abuse is responsible for this phenomenon or merely enhances an ageing-specific process, our findings suggest that hypermethylation in alcohol-dependent patients is a consequence, rather than a cause, of the disorder